DESCRIPTION Adapted from applicant's abstract): Aging is accompanied by a slow decline in cognitive function, now referred to as mild cognitive impairment (MCI), and by accumulation of oxidized proteins and lipids as a result of oxidative stress. Eukarion has discovered a new class of manganese complexes that display both superoxide dismutase (SOD) and catalase activities. These SOD/catalase mimetics have shown efficacy in several models of human diseases in which oxidative stress has been implicated. In particular, EUK-134 has been found to be highly protective in a rodent model for stroke and in kainic acid-induced neuronal damage. It also reduced oxidative stress and prolonged survival in a mouse model for ALS. The present project is directed at testing the efficacy of EUK-134 and another analog on age-related oxidative stress and learning and memory impairment in mice. Eight month-old mice will be treated with EUK-134 and another analog for 3 months. They will be tested for acquisition and retention of 2 different tasks, an avoidance learning paradigm, and a fear-conditioning paradigm. Markers of oxidative stress will be measured in various brain structures and correlated with behavioral measures. It is our hope that results from these studies will demonstrate the potential therapeutic values of EUK molecules for treating patients with MCI. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE